A Comparison of Monotherapy and Combination Therapy With Antipsychotic Medications for Intensive Care Unit Delirium: A Retrospective Cohort Study

Ann Pharmacother. 2026 Jan;60(1):5-14. doi: 10.1177/10600280251322199. Epub 2025 May 6.

Abstract

Background: Antipsychotic medications continue to be frequently prescribed by clinicians in the intensive care unit (ICU) for delirium, despite inconclusive data.

Objective: To determine if using a combination of antipsychotics reduces the time patients spend in delirium compared with monotherapy.

Methods: This was a single-center, retrospective, cohort medical record review of patients who scored positive on Confusion Assessment Method for the ICU (CAM-ICU) and received antipsychotic therapy. Patients were excluded if they received any antipsychotics prior to hospital admission or had a Richmond Agitation-Sedation Scale (RASS) scores of -4 or -5 at the time of CAM-ICU assessment. The primary outcome was duration of delirium. The secondary outcomes included ICU length of stay (LOS), hospital LOS, overall mortality, occurrence of adverse events (AEs), and whether antipsychotics were continued at hospital discharge.

Results: A total of 84 patients were included, of these 45 and 39 received monotherapy and combination therapy, respectively. Median Acute Physiology and Chronic Health Evaluation II (APACHE II) scores were significantly higher in the monotherapy group (18 vs 13, P = 0.006). Median duration of delirium was not significantly different between the monotherapy and combination therapy groups (8 vs 8 days, P = 0.932). Median ICU and hospital LOS, and occurrence of AEs were not significantly different. A significant difference in mortality was found between monotherapy and combination therapy (31% vs 10%, P = 0.02). Antipsychotics were continued at hospital discharge in 64% of the monotherapy and in 44% of the combination therapy group.

Conclusion and relevance: In patients with ICU delirium, there was no difference in duration of delirium among patients receiving monotherapy compared with combination therapy with antipsychotics, though they may be sicker and have a higher mortality. Patients commonly remain on antipsychotics at hospital discharge, the implications of which warrant further study.

Keywords: CAM-ICU; antipsychotic agents; critical care; delirium; intensive care unit.

Publication types

  • Comparative Study

MeSH terms

  • Aged
  • Antipsychotic Agents* / administration & dosage
  • Antipsychotic Agents* / adverse effects
  • Antipsychotic Agents* / therapeutic use
  • Cohort Studies
  • Delirium* / drug therapy
  • Drug Therapy, Combination
  • Female
  • Humans
  • Intensive Care Units*
  • Length of Stay / statistics & numerical data
  • Male
  • Middle Aged
  • Retrospective Studies

Substances

  • Antipsychotic Agents